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Table of Contents

Introduction
Urinary Tract Infections in Women
Urinary Tract Infections in Men
Phage Therapy Center Treatment of Urinary Tract Infections
References

Introduction

Urologic diseases encompass a wide scope of illnesses of the genitourinary tract, including conditions that are congenital and acquired, malignant and benign, male and female, medical and surgical. They can occur at any point in the course of human development, from hydronephrosis in utero to urinary incontinence in the elderly. They may be acute and self-limited or chronic and debilitating, may primarily affect quality or quantity of life, and may be financially insignificant or catastrophic. Some urologic diseases present with complex signs and symptoms and require extensive evaluation, while others present with classical symptoms and are easily diagnosed. Still others occur without any symptoms at all and are discovered incidentally or during screening. For many urologic diseases the etiology is well understood, and the natural history is fairly predictable.

Urinary tract infection (UTI) is caused by pathogenic invasion of the urinary tract, which leads to an inflammatory response of the urothelium. Infections may be acute or chronic. The clinical manifestations of UTI depend on the portion of the urinary tract involved, the etiologic organism(s), the severity of the infection, and the patient’s ability to mount an immune response to it. Signs and symptoms may include fever, chills, dysuria, urinary urgency, frequency, and cloudy or malodorous urine.

Infections in the urinary system are often classified by the anatomic site or organ involved, although the entire urinary tract may be affected. Urinary tract infections are among the most common urological disorders in both men and women. A variety of forms of UTI are recognized, and they may differ significantly, by location and severity. Overall, approximately 20%of all UTIs occur in men. These infections result in significant financial and personal costs for both individual patients and the health care system.

Pyelonephritis refers to a urinary tract infection involving the kidney. This may be an acute or chronic process. Acute pyelonephritis is characterized by fever, chills, and flank pain. Patients may also experience nausea and vomiting,depending on the severity of the infection and whether there is any obstruction to the flow of urine out of the renal collecting system.The risk of renal damage in most patients with uncomplicated UTI is low,even in those with uncomplicated acute pyelonephritis. Chronic pyelonephritis implies recurrent renal infections and may be associated with the development of renal scarring and impaired function if obstruction is present. A perinephric abscess may develop in severe cases of pyelonephritis. The clinical distinction between upper and lower UTI may be difficult, particularly in women.

Cystitis is an inflammatory process of the urinary bladder, typically caused by bacterial infection. It may be acute or chronic in nature. Urethritis refers to an inflammation or infection of the urethra. This often occurs in combination with cystitis and may be difficult to differentiate. Isolated bacterial urethritis is rare in women. Vaginitis and cervicitis, often related to sexually transmitted organisms, may also cause symptoms attributed to cystitis or urethritis.

Urinary tract infections may be associated with significant morbidity and even mortality. This is particularly true in the frail elderly and in those with associated urinary incontinence,where UTI may be related to skin breakdown and ulceration. Complicated UTIs may lead to urosepsis and death.

Urinary Tract Infections in Women

Women are at greater risk for UTI than men, partly because of the relatively short, straight anatomy of the urethra.Retrograde ascent of bacteria from the perineum is the most common cause of acute cystitis in women. Host factors such as changes in normal vaginal flora may also affect the risk of UTI.Sexually active women are at greater risk for UTI than women who do not engage in sexual intercourse.

Recurent UTI's involve reinfection from a source outside the urinary tract or from bacterial persistence within it. In each case, the infections may be caused by the same or different organisms. The vast majority of recurrent UTI's in women are due to reinfection.

Post-menopausal women are at higher risk for UTI than younger women are, because they lack estrogen, which is essential to maintain the normal acidity of vaginal fluid. This acidity is critical to permit the growth of Lactobacillus in the normal vaginal flora, which acts as a natural host defense mechanism against symptomatic UTI.Restoration of the normal hormonal milieu in the vagina is not effective treatment for active urinary tract infections, but it may be useful for prevention. Other urologic factors potentially associated with an increased risk of UTI in post-menopausal women include urinary incontinence, cystocele, and elevated volumes of post-void residual urine.

Urinary tract infections are often characterized as uncomplicated if they involve only the bladder and are not associated with the presence of foreign bodies or anatomic abnormalities. Complicated UTIs may include pyelonephritis, urosepsis and the presence of foreign bodies or anatomic disorders. Significant UTIs in elderly patients are often classified as complicated due to the increased risk of associated morbidity and mortality in this population.

Urinary tract infections may be caused by a variety of different organisms, most commonly bacteria. The most frequent bacterial cause of UTI in adult women is Escherichia coli, which is part of the normal gut flora. This organism accounts for approximately 85% of community-acquired UTIs and 50% of hospital-acquired UTIs. Other common organisms include Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus saprophyticus and Proteus spp..  Nosocomial infections and those associated with foreign bodies may involve more aggressive organisms such as Pseudomonas aeruginosa, Serratia, Enterobacter, and Citrobacter species.

Nonbacterial infections are less common and tend to occur more often in immunosuppressed individuals or those with diabetes mellitus. Fungal infections with Candida spp are the most common nonbacterial infections. Other less common urinary tract infections include Mycobacterium tuberculosis and a variety of anaerobic organisms. The overall role of anaerobic urinary infections is controversial; however, anaerobic urinary infections is controversial; however, anaerobes may be especially dangerous in immunocompromised patients due to an increased risk of severe infections such as emphysematous pyelonephritis or cystitis.

Urinary tract infection is an extremely common diagnosis in women, and treatment incurs substantial costs. It is estimated that at least one-third of all women in the United States are diagnosed with a UTI by the time they reach 24 years of age (3). In a random-digit-dialing telephone survey of 2,000 women, Foxman and colleagues found that 10.8% of women 18 years of age or older self-reported at least one UTI in the previous 12 months (95%CI, 9.4 –12.1) .Using this information, the authors calculated the lifetime risk for UTI in their sample to be 60.4%. Using these data, the authors estimated that at least 11.3 million women in the United States had at least one UTI in 1995, and the overall cost of prescriptions to treat UTIs that year was more than $218 million.

Inpatient services accounted for the majority of treatment costs, although the fraction of expenditures devoted to inpatient care declined over time. Total spending on UTIs for women, after adjustment for inflation, increased about 1% per year between 1994 and 2000. The biggest percentage increases in spending were for services provided in physician offices and ERs. Most of the UTI-related expenditures in Medicare beneficiaries were for inpatient services. The bulk of this spending was for women over 65, although UTI-related expenditures exceeded $100 million in 1998 among Medicare enrollees under 65, primarily the disabled. This does not include expenditures for complementary and alternative therapies, which may be substantial, given widespread beliefs in such remedies as cranberry juice. The mean annual health care expenditures for privately insured women with a diagnosis of UTI in 1999 were approximately 1.4 times higher than those for women without UTI. Although similar across regions, the estimated overall costs in the South were the highest in the United States. Patient age did not appear to be a significant factor in health care expenditures in 1999.

Urinary Tract Infections in Men

As described above, male anatomic structures that may be involved with infectious processes include the prostate, testis, scrotum, and epididymis.

Approximately 20% of all UTIs occur in men. Between 1988 and 1994,the overall lifetime prevalence of UTI in men was estimated to be 13,689 cases per 100,000 adult men, based on the National Health and Nutrition Examination Survey. In comparison, the estimate for women was 53,067 cases per 100,000 adult women during the same time period.

Urinary tract infections in men are associated with a significant economic cost. Adjusted mean health care expenditures for privately insured men diagnosed with a UTI was $5,544 in 1999, while the expenditure was $2,715 for men who did not experience a UTI. In adults without a UTI, annual health care expenditures were lower for men than for women ($2,715 versus $3,833, respectively). However, there is little difference in total annual health care expenditures for men and women with UTI ($5,544 vs $5,407).

Phage Therapy Center Treatment of Urinary Tract Infections

Phage Therapy Center tends to receive patients who have run out of options, where antibiotic therapy is no longer effective.

In Stuart Levy's book, The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle, Levy describes how the continued use of antibiotics tends to "select out" those bacteria that are resistant to the antibiotic.  In other words, the antibiotic destroys all but the resistant bacteria, giving the appearance that the antibiotic stops working, the infection "comes back" or "recurs" after a period of time. Levy also shows that bacteria in a given infection can exchange resistance capabilities very rapidly and directly from other bacteria of the same species and from different species, causing the infection to change in terms of resistance over a short period of time. This may explain one of the mechanisms of recurrent UTI's.

At Phage Therapy Center it is understood that a primary cause of chronic infection is the formation of colonies of multiple species of pathogenic and non-pathogenic microorganisms called "biofilm". These complex mixtures of microbes (biofilms) typically resist the effects of antibiotics, which otherwise kill rapidly dividing planktonic bacteria of the same species.

Bacteriophages are particularly effective for treating urinary infections. Combinations of phages called "phage cocktails" are the main medication used during treatment. Phage cocktails work in a manner similar to the antibiotic/drug cocktails are employed by an infectious disease specialist to treat a resistant infection: in these cases, more than one drug is used to control or eliminate the infection. In theory, those bacteria that are not sensitive to one of the drugs tend to be sensitive to the other.  Phage cocktails typically contain a minimum of three and usually more many phages that are effective for a given bacterial species.  Unlike antibiotics, bacteriophages are able to break down biofilms. Phage cocktails have been shown to be very efficient at eliminating resistant strains and, given a high enough concentration, the phage cocktail will even evolve its effectiveness at a rate faster than the bacteria can acquire resistance characteristics from other bacteria involved or associated with the infection, or from the environment.

Because UTI's represent a wide range of conditions -- some that are potentially not caused by bacterial infection, Phage Therapy Center's treatment must always begin with a urine sample. This is required in order to detect what bacteria is causing the infection. This sample must sent to our laboratory several weeks prior to coming for treatment. Our laboratory grows the isolated strains and tests to be sure that the infection is sensitive to the commercial bacteriophage cocktail; if it is not sufficiently sensitive, then a custom phage cocktail (autophage) must be prepared for the patient. It is also desirable that the patient provide a medical report. If no infection is indicated in the sample, the patient should contact the Phage Therapy Center staff for additional instructions.

When the patient arrives at the clinic, a new sample is taken and tested; a complete examination is provided. Urine samples will be tested throughout the treatment to determine if the infection has changed and to verify that the phage cocktail remains effective.

In general, chronic urinary infections can requires a minimum of two weeks of outpatient care to complete. In some cases, as the biofilms clear and the dominant pathogens are eliminated, others pathogenic bacteria that did not initially show up in laboratory cultures may present in the urine sample. The clinic will re-test and match phages with these strains. This process may need to be repeated several times, until the infection is completely cleared, depending on the individual. Therefore, the patient should be prepared to stay at the clinic for the entire course of treatment in order to receive the best treatment results.

References

Urologic Diseases in America
National Institute of Diabetes and Digestive and Kidney Diseases

The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle
By Stuart B. Levy. 279 pp., illustrated. New York, Plenum, 1992. $24.95. ISBN 0-306-44331-7.